A HYPOTHALAMIC NEURONAL CELL-LINE PERSISTENTLY INFECTED WITH SCRAPIE PRIONS EXHIBITS APOPTOSIS

Neuronal death and vacuolation are characteristics of the CNS degenera tion found in prion diseases. Relatively few cultured cell lines have been identified that can be persistently infected with scrapie prions, and none of these cells show cytopathologic changes reminiscent of pr ion neuropathology. The differentiated neuronal cell line GT1, establi shed from gonadotropin hormone releasing-hormone neurons immortalized by genetically targeted tumorigenesis in transgenic mice (P. L. Mellon , J.J. Windle, P. C. Goldsmith, C. A. Padula, J. L. Roberts, and R. I. Weiner, Neuron 5:1-10, 1990), was examined for its ability to support prion formation. We found that GT1 cells could be persistently infect ed with mouse RML prions and that conditioned medium from infected cel ls could transfer prions to uninfected cells. In many but not all expe riments, a subpopulation of cells showed reduced viability, morphologi cal signs of neurodegeneration and vacuolation, and features of apopto sis. Subclones of GT1 cells that were stably transfected with the trkA gene encoding the high-affinity nerve growth factor (NGF) receptor (G T1-trk) could also be persistently infected. NGF increased the viabili ty of the scrapie-infected GT1-trk cells and reduced the morphological and biochemical signs of vacuolation and apoptosis. GT1 cells represe nt a novel system for studying the molecular mechanisms underlying pri on infectivity and subsequent neurodegenerative changes.